The
New Math of Corneal StainingHom, Milton M. OD, FAAO

The
latest method for grading corneal staining may not always provide
valid results.

We're all
familiar with corneal staining. You wet the strip, instill
fluorescein and observe using blue light and sometimes a yellow
filter. You can look at the amount and location of staining, if at
all present. You make a note and move on to the rest of the
examination.

I used to
think this was a relatively simple procedure. But if you scan the
recent literature, you'll find that corneal staining has become the
subject of a contact lens solutions controversy of numbers, grids
and diagrams. Any practitioner with even a mild interest in contact
lenses can't avoid the recent blitz of studies and statements. All
of a sudden, this simple procedure has become incredibly complex
with phenomenal nuances and sometimes unbelievable implications.

Causes and Consequences of Staining

Efron
(2004) divides staining into six causes: mechanical, exposure,
metabolic, toxic, allergic and infectious. Why is corneal staining
important? The basic reason is that it forms a theoretical pathway
to infection. A break in the epithelium is the first step for
bacteria to get a foothold into the cornea. Jalbert et al (2006)
demonstrated that large-area solution toxicity staining, covering
four out of five corneal zones, is more likely to have corneal
infiltrates.

On the
other hand, the connection between infection and staining may be
questionable. Willcox and Holden (2001) state, There needs to be
damage to the epithelium in order for bacteria to initiate
infection. The supporting reference from Klotz et al (1989) reports
on an animal model of epithelial damage by filter paper.

Some of
the recent literature omits the simple fact that corneal staining
has a multitude of other causes and effects. Low-level corneal
staining in itself doesn't mean there's a problem at hand. Efron
(2004) and Guillon et al (1990) reported staining as high as 60
percent for contact lens wearers, but it's often low-level and
clinically insignificant. As most fitters know, corneal staining can
be normal. Several studies have found the mean grade for successful
contact lens wearers to be 0.5 or less. Low-level staining of less
than Grade 2 doesn't necessarily require action. For most patients,
walking through life with Grade 1+ staining is a non-event rather
than a crisis.

Clinical Significance and Grades

Researchers have used several grading systems to describe and
quantify corneal staining. In the past, corneal staining was
evaluated with 5 grades (0 to 4) over the entire cornea.
Fortunately, systems have evolved. Most current classification
systems divide the cornea into five zones: central, superior,
inferior, nasal and temporal. Each zone is graded separately. The
more sophisticated systems specify the number of punctate dots per
zone. Other systems classify each zone with Grades 0 to 4 or
something similar.

Despite
their best intentions, clinical significance can sometimes be
ambiguous. Let's consider some of the studies playing a role in this
solutions war.

Grading Scales

One
grading system garnering much attention is the Staining Grid, which
divides the cornea into the typical five zones but grades on a
percentage basis (0 percent, 10 percent, 20 percent, etc). The
cut-offs for each percentage can be problematic. Let's say that less
than 30 punctate or dots is 0 percent and 30 dots or more denotes 10
percent. In this case, 30 punctate is the cutoff between no staining
and 10 percent staining. Here are some examples of how this method
can be misleading.

Example 1: Zero Percent
Grade

A dot
cluster may be graded incorrectly if it falls between two sectors.
In Figure 1, the 30+ dot cluster
is considered 0 percent and 0 percent because each sector contains
about 15 dots. I would think that we should consider the staining in
this example as more than 0 percent and 0 percent.

Figure 1. If the dot cluster
is greater than 30 punctate, but falls between two
sectors, it would be considered 0 percent.

Example 2: One Plus One
Equals One

Along the
same lines, two clusters may be almost equal in size, but one would
be counted and the other would not. In
Figure 2, the cluster for the left sector has 29 dots (graded as
0 percent) and the cluster in the right sector has 30 dots (graded
as 10 percent).

Figure 2. Two clusters of
equal size are shown. One would be counted, the other
would not because it has less than 30 dots.

Example 3: Is It Always the
Solution?

Suppose
the dots are located only in the inferior sector. Typically,
staining from conditions such as dry eye or from distribution
problems commonly occurs in the inferior sector. You would grade the
staining in Figure 3 as 10
percent, but the cause could be something different from
solution-related sensitivity. Also, in the previous Example 2, you
may misinterpret three o'clock and nine o'clock staining as
solution-related staining.

Figure 3. This cluster would
be graded as 10 percent, but the cause could be
something different from solution sensitivity.

Example 4: Peripheral Dots

The dots
in Figure 4 are located around the
periphery, but number below the cutoff of 30 punctate for each
sector. Under the Staining Grid system you'd grade the staining as 0
percent for all sectors. However, many solution sensitivity types of
staining are located around the periphery.

Figure 4. The peripheral
staining in this example would be graded as 0 percent
under the grading system discussed.

Statistical Significance

Researchers perform statistical tests to determine if a finding is
actually significant. P-values equal to or less than 0.05 are
considered statistically significant. In biostatistics, p-values are
needed to validate a claim. You may see very large percentages, but
if the readings have a wide variability and range (large standard
deviations), it may not have statistical significance.

In the
Staining Grid poster presentation (Andrasko, 2006), no p-values
accompany the percentages. Although the percentages may be large in
some combinations, a p-value is necessary to determine significance.
Hopefully we'll see this information in the future.

Karpecki
(2006) identified another example in which we could question
statistical significance. A recent study suggests that ReNu
MultiPlus (Bausch & Lomb) was associated with significant reduction
in relative corneal sensitivity compared to Opti-Free Express
(Alcon). They enrolled only four patients within each arm of the
study, making an extremely small sample. Another confounding
variable arises from the researchers' decision to include outliers
within the final data set. One of the aesthesiometry readings in
this study was significantly lower (20.00) than that of all the
other data in either group. From a clinician's perspective, if you
have a reading of 20 in one case when all the other measurements
averaged 82.86 (with 100 percent representing the highest degree of
comfort), you could come to the obvious conclusion that the patient
registering a 20 would have trouble wearing contact lenses to begin
with. As a result, most researchers would classify this particular
data point as an outlier that they should footnote, but exclude from
the final study results. If they had followed those scientific
steps, the result would likely have shown no statistical difference
between the solutions.

Other
studies show quite the opposite staining response. In one
open-label, multicenter study, researchers switched satisfied
hydrogel (615 subjects) and silicone hydrogel (19 subjects) contact
lens wearers from their habitual lens care product to ReNu MultiPlus.
They recruited current users of Opti-Free Express or Complete
(Advanced Medical Optics) multipurpose solutions. Graded slit lamp
evaluation showed fewer statistically significant (P<0.05)
occurrences of epithelial edema, epithelial microcysts, corneal
staining, limbal injection, bulbar injection, tarsal conjunctival
abnormalities, neovascularization and infiltrates associated with
the use of ReNu MultiPlus compared with the subjects' habitual
solutions (Figure 5). Since the
introduction of the original ReNu MPS formula, the incidence of
infectious keratitis, as reported by Poggio et al in 1989 and Cheng
et al in 1999 hasn't increased. Over the past almost 20 years during
which PHMB solutions in general have become the principal choice of
tens of millions of contact lens wearers worldwide, a recent PubMed
search reveals that no increase in the incidence of contact
lens-related microbial keratitis has occurred.

Consider Results Carefully

Unfortunately, some of the conclusions from the aforementioned
studies may bring about unwarranted fear about corneal staining for
patients. History shows that medical scares are nothing new
(cell-phone-induced brain cancer, acrylamide in potato chips and
Alar in our food supply). Hopefully the new math won't add corneal
staining to that list.

Dr. Hom
is the author of Manual of Contact Lens Prescribing and Fitting with
CD-ROM Second Edition and LASIK: Clinical Co-Management. He
practices in Azusa, Calif.